Medicine and Health Sciences Commons^™

Whole Genome Sequence Analysis Of Low-Density Lipoprotein Cholesterol Across 246 K Individuals, Margaret Sunitha Selvaraj, Lisa De Las Fuentes, Susan K. Dutcher, Et Al.

2020-Current year OA Pubs

No abstract provided.

Microbial Degradation Of Persistent Organic Pollutants In Food Supply Chain, Pankaj Kumar, Ajay Singh, Manikant Tripathi, Deepti Diwan, R Manimekalai, Minaxi Sharma, Sudisha Jogajah, Ramesh Chandra Dubey, Gauri Dutt Sharma

2020-Current year OA Pubs

No abstract provided.

Assessing The Clinical Meaningfulness Of Slowing Cdr-Sb Progression With Disease-Modifying Therapies For Alzheimer's Disease, Sarah M Hartz, Suzanne E Schindler, Marissa L Streitz, Krista L Moulder, Jessica Mozersky, Guoqiao Wang, Chengjie Xiong, John C Morris

2020-Current year OA Pubs

INTRODUCTION: For many patients and caregivers, a major goal of disease-modifying treatments (DMTs) for Alzheimer's disease (AD) dementia is to extend independence in instrumental and basic activities of daily living (IADLs and BADLs). The goal of this study was to estimate the effect of treatments on the time remaining independent in IADLs and BADLs.

METHODS: Participants at the Knight Alzheimer Disease Research Center (Knight ADRC) who met eligibility criteria for recent DMT trials were studied: age ≥60 years at baseline, clinical diagnosis of very mild or mild AD dementia (global Clinical Dementia Rating [CDR] score 0.5 or 1), biomarker confirmation …

Schistosomiasis Interventions In Africa: Assessment And Systematic Review, Christopher Yaw Dumevi, George Boateng Kyei, Patience B Tetteh-Quarcoo, James-Paul Kretchy, Irene Ayi, Patrick F Ayeh-Kumi

2020-Current year OA Pubs

No abstract provided.

System Readiness And The Patient Care Pathway For Alzheimer's Disease Diagnosis And Treatment, B Joy Snider, Et Al.

2020-Current year OA Pubs

Promising therapeutic interventions that target the underlying pathophysiology are changing the landscape of Alzheimer's disease (AD) research. The AD care pathway must be transformed to meet the challenge of bringing these new therapies to the increasing number of people living with AD within the existing healthcare framework. Challenges include identifying patients who may benefit from treatment interventions early in the course of the disease, ensuring that diagnostic tools are accessible and accurate, and developing capabilities to monitor the effectiveness of interventions over time. These challenges must be addressed at all levels, from primary care settings to tertiary treatment centers; this …

Psychosocial Behavioral Phenotypes Of Racially/Ethnically Minoritized Older Adults Enrolled In Habs-Hd Differ On Neuroimaging Measures Of Brain Age Gap, Hippocampal Volume, And Cortical Thickness, Alexandra L Clark, Makenna B Mcgill, Alexandra J Weigand, Julie K Wisch, Kalen Petersen, Beau Ances, Meredith N Braskie, Sid O'Bryant, Kelsey R Thomas, Habs‐Hd Study Team

2020-Current year OA Pubs

INTRODUCTION: This study examined whether previously identified psychosocial behavioral phenotypes differed on structural neuroimaging markers.

METHODS: Latent profile analysis (LPA) employed in a sample of 1820 community-dwelling older adults (1118 Hispanic and 702 Black) replicated previous Low Resource/Low Distress, High Resource/Low Distress, and Low Resource/High Distress phenotype classifications. Analyses of covariance (ANCOVAs) adjusting for relevant factors examined phenotype differences on neuroimaging outcomes of predicted brain age gap (BAG) (DeepBrainNet

RESULTS: The Low Resource/Low Distress and Low Resource/High Distress phenotypes had significantly higher predicted BAGs relative to the High Resource/Low Distress phenotype, and the Low Resource/High Distress group displayed significantly lower …

Proceedings Of The 12th Annual Deep Brain Stimulation Think Tank: Cutting Edge Technology Meets Novel Applications, Alfonso Enrique Martinez-Nunez, Nico U F Dosenbach, Evan M Gordon, Et Al.

2020-Current year OA Pubs

The Deep Brain Stimulation (DBS) Think Tank XII was held on August 21st to 23rd. This year we showcased groundbreaking advancements in neuromodulation technology, focusing heavily on the novel uses of existing technology as well as next-generation technology. Our keynote speaker shared the vision of using neuro artificial intelligence to predict depression using brain electrophysiology. Innovative applications are currently being explored in stroke, disorders of consciousness, and sleep, while established treatments for movement disorders like Parkinson's disease are being refined with adaptive stimulation. Neuromodulation is solidifying its role in treating psychiatric disorders such as depression and obsessive-compulsive disorder, particularly for …

Methylome Analysis Of Ftld Patients With Tdp-43 Pathology Identifies Epigenetic Signatures Specific To Pathological Subtypes, Cristina T. Vicente, Cyril Pottier, Carlos Cruchaga, Et Al.

2020-Current year OA Pubs

No abstract provided.

Effects Of Vagus Nerve Stimulation On Daily Function And Quality Of Life In Markedly Treatment-Resistant Major Depression: Findings From A One-Year, Randomized, Sham-Controlled Trial, A John Rush, Charles R Conway, Et Al.

2020-Current year OA Pubs

BACKGROUND: Depression treatments aim to minimize symptom burden and optimize quality of life (QoL) and psychosocial function.

OBJECTIVE: Compare the effects of adjunctive versus sham vagus nerve stimulation (VNS) on QoL and function in markedly treatment-resistant depression (TRD).

METHODS: In this multicenter, double-blind, sham-controlled trial, 493 adults with TRD and ≥4 adequate but unsuccessful antidepressant treatment trials (current episode) were randomized to active (n = 249) or sham (n = 244) VNS (plus treatment as usual) over a 12-month observation period. Quarterly outcomes included QoL with the Q-LES-Q, Mini-Q-LES-Q, and EQ-5D-5L, and function with the WHODAS 2.0 and Work Productivity …

Exploring Factors Contributing To Patient Decision-Making In The Care Journey To Elective Hernia Care In Kenya, Helen W. Li, Jesse Kiprono Too, Sarah Nyanchama Nyariki, Charles Nathan Nessle, Sara Malone, Rachel Matsumoto, Teddy Ashibende Aurah, Jeffrey A. Blatnik, Joanna Hunter-Squires, Ivan Seno Saruni

2020-Current year OA Pubs

BACKGROUND: Capacity for elective general surgical care is an important reflection of a health system's ability to meet a population's surgical needs and is currently known to be inadequate in many low- and middle-income countries. Patient agency is a key, understudied factor which shapes how and when patients ultimately decide to engage with formal care. Understanding factors which influence patient care seeking activity can have important implications for how current and future health systems may be utilized. This study aims to explore how patients approach the navigation and triage of their elective hernia condition within the Kenyan surgical care system. …

Recombinant Human Alpha-N-Acetylglucosamine-6-Sulfatase Delivered To Sanfilippo D Mice With Repeated Intracerebroventricular Injections Corrects Cns Pathology, Grant L. Austin, Feng Wang, Steven Q. Le, Alexander Sorensen, Shan Li, Lai C. Foong, Srikanth Singamsetty, Jill Wood, Tsui-Fen Chou, Patricia I. Dickson

2020-Current year OA Pubs

Mucopolysaccharidosis type IIID (MPS IIID; Sanfilippo D) is caused by biallelic pathogenic variants in N-acetylglucosamine-6-sulfatase (GNS), which participates in catabolism of heparan sulfate (HS) glycosaminoglycans. Characterization of MPS IIID disease at a cellular level has not been robustly achieved. We used unbiased quantitative proteomics to establish a cellular phenotype for MPS IIID mice. Recombinant human GNS (rhGNS), a variant of which previously demonstrated single dose efficacy in MPS IIID human fibroblasts and in MPS IIID neonatal mice, was used to establish a repeat dosing schedule to treat MPS IIID mice. Adult Gns KO mice or heterozygous carriers were treated via …

Preliminary Investigation Of Obstructive Sleep Apnea And Alzheimer's Disease In Down Syndrome, Dasoo M Yoon, David T Plante, Victoria Fleming, Benjamin Handen, Patrick Lao, Jamie Peven, Bradley Christian, Ozioma Okonkwo, Charles Laymon, Beau Ances, Christy Hom, Brian Helsel, Sigan L Hartley

2020-Current year OA Pubs

This study provided a preliminary examination of indices of obstructive sleep apsnea (OSA) and sleep disruptions in adults with Down syndrome (DS), and their associations with Alzheimer's disease (AD) pathology and symptomatology. A total of 93 adults with DS (aged 25-61 years) from the Alzheimer Biomarker Consortium-DS completed cognitive assessments, MRI and positron emission tomography (PET) scans (assessing amyloid-beta [Aβ] and tau), and a one-night home sleep study using the WatchPAT-300 device. Study partners also reported on depressive symptoms and diagnoses. Correlational analyses examined relationships between sleep variables, PET biomarkers, and AD symptomatology (cognitive functioning and depressive mood), controlling for …

Measuring Stigma In Pediatric Oncology: A Cross-Sectional Analysis Of Three Global Sites, Lara E Counts, Sara M Malone, Et Al.

2020-Current year OA Pubs

PURPOSE: Stigma contributes to fear and shame, resulting in delays in care-seeking behavior among individuals with cancer. As a social construct, stigma is affected by language, religion, culture, and local norms. This study explored pediatric cancer stigma at the time of diagnosis across diverse settings through the adaptation of two stigma measures.

METHODS: This study was conducted with adolescents and caregivers of children with osteosarcoma and retinoblastoma at three centers in Jordan, Guatemala, and Zimbabwe. The Stigma-related Social Problems (SSP) and the eight-item Stigma Scale for Chronic Illness (SSCI-8) measures were translated into Arabic, Spanish, and Shona and contextually adapted …

Structural Diversity Of Axonemes Across Mammalian Motile Cilia, Miguel Ricardo Leung, Chen Sun, Jianwei Zeng, Jacob R Anderson, Qingwei Niu, Wei Huang, Willem E M Noteborn, Alan Brown, Tzviya Zeev-Ben-Mordehai, Rui Zhang

2020-Current year OA Pubs

Reproduction, development and homeostasis depend on motile cilia, whose rhythmic beating is powered by a microtubule-based molecular machine called the axoneme. Although an atomic model of the axoneme is available for the alga Chlamydomonas reinhardtii

Slc35a2 Gene Product Modulates Paramyxovirus Fusion Events During Infection, Yanling Yang, Yuchen Wang, Danielle E. Campbell, Heng-Wei Lee, Wandy Beatty, Leran Wang, Megan Baldridge, Carolina B. López

2020-Current year OA Pubs

Paramyxoviruses are significant human and animal pathogens that include mumps virus (MuV), Newcastle disease virus (NDV) and the murine parainfluenza virus Sendai (SeV). Despite their importance, few host factors implicated in paramyxovirus infection are known. Using a recombinant SeV expressing destabilized eGFP (rSeVCdseGFP) in a loss-of-function CRISPR screen, we identified the CMP-sialic acid transporter (CST) gene SLC35A1 and the UDP-galactose transporter (UGT) gene SLC35A2 as essential for paramyxovirus infection. As expected, SLC35A1 knockout (KO) cells showed drastic reduction in infections with SeV, NDV and MuV due to the lack of cell surface sialic acids receptors. However, SLC35A2 KO cells revealed …

Prevention And Management Of Posterior Wound Complications Following Oncologic Spine Surgery: Narrative Review Of Available Evidence And Proposed Clinical Decision-Making Algorithm, Owen P Leary, Matthew L Goodwin, Et Al.

2020-Current year OA Pubs

STUDY DESIGN: Narrative Review.

OBJECTIVE: Contextualized by a narrative review of recent literature, we propose a wound complication prevention and management algorithm for spinal oncology patients. We highlight available strategies and motivate future research to identify optimal and individualized wound management for this population.

METHODS: We conducted a search of recent studies (2010-2022) using relevant keywords to identify primary literature in support of current strategies for wound complication prevention and management following spine tumor surgery. When primary literature specific to spine tumor cases was not available, data were extrapolated from studies of other spine surgery populations. Results were compiled into …

Aav Gene Therapy For Duchenne Muscular Dystrophy: The Embark Phase 3 Randomized Trial, Jerry R Mendell, Craig M Zaidman, Et Al.

2020-Current year OA Pubs

Duchenne muscular dystrophy (DMD) is a rare, X-linked neuromuscular disease caused by pathogenic variants in the DMD gene that result in the absence of functional dystrophin, beginning at birth and leading to progressive impaired motor function, loss of ambulation and life-threatening cardiorespiratory complications. Delandistrogene moxeparvovec, an adeno-associated rh74-viral vector-based gene therapy, addresses absent functional dystrophin in DMD. Here the phase 3 EMBARK study aimed to assess the efficacy and safety of delandistrogene moxeparvovec in patients with DMD. Ambulatory males with DMD, ≥4 years to <8 years of age, were randomized and stratified by age group and North Star Ambulatory Assessment (NSAA) score to single-administration intravenous delandistrogene moxeparvovec (1.33 × 10

Cancer-Targeted Pro-Theranostic Bi-Metallic Organo-Coordination Nanoparticles, Hengbo Huang, Lei Fang, Janaka Wansapura, Julie L Prior, Brad Manion, Baogang Xu, Cody Hongsermeier, Nisha Gamadia, Nicole Blasi, Rui Tang, Christopher Egbulefu, Monica Shokeen, James D Quirk, Samuel Achilefu

2020-Current year OA Pubs

No abstract provided.

Cause Of Death For Heart Transplant Patients, An Autopsy Study, Justin Burk, Cory T Bernadt, Jon Ritter, Chieh-Yu Lin

2020-Current year OA Pubs

INTRODUCTION: Heart transplantations are lifesaving for patients with end-stage heart failure. It is pertinent for the multidisciplinary care team to understand how heart transplant patients succumbed to death and the complications that occurred. In this study, we performed a comprehensive retrospective review of all the autopsies performed in our institute for heart transplant patients and report the trend of demographic data, cause of death, and autopsy findings.

MATERIALS AND METHODS: Reports, photos, and slides of autopsies performed at our institute from 1990 to 2023 for heart transplant patients were reviewed. Pertinent demographic data (age, gender, pretransplant diagnosis), clinical data (clinical …

Revisiting Abdominal Wall "Morbidity" Of The Extensile Anterolateral Approach To The Thoracolumbar Spine, Alekos A Theologis, Andrew P Collins, Kanwar Parhar, Munish C Gupta

2020-Current year OA Pubs

PURPOSE: To assess patients' perceptions of their abdominal wall following extensile anterolateral approaches to the thoracolumbar spine for adult spinal deformity (ASD) using validated questionnaires.

METHODS: Adults who underwent anterior-posterior thoracolumbar spinal operations to the pelvis for ASD in which the anterior fusion was performed through an extensile anterolateral approach were reviewed. Three questionnaires were administered at least 1 year following surgery and included The Abdominal Core Health Quality Collaborative Survey (AHS-QC), The Patient Scar Assessment Scale (PSAS), and The Anterior Abdominal Incision Questionnaire (AAIQ).

RESULTS: Fifty-one patients (80.4% female, median age 65 years) were included. Average follow-up was 2.8 …

Novel Loci For Triglyceride/Hdl-C Ratio Longitudinal Change Among Subjects Without T2d, Lihua Wang, Siyu Wang, Jason A Anema, Vaha A Moghaddam, Yanli Lu, Shiow Lin, E Warwick Daw, Allison L Kuipers, Iva Miljkovic, Michael Brent, Gary J Patti, Bharat Thygarajan, Joseph M Zmuda, Michael A Province, Ping An

2020-Current year OA Pubs

Triglyceride (TG)/HDL-C ratio (THR) is a surrogate predictor of hyperinsulinemia. To identify novel genetic loci for THR change over time (ΔTHR), we conducted genome-wide association study (GWAS) and genome-wide linkage scan (GWLS) among nondiabetic Europeans from the Long Life Family Study (n = 1,384). Subjects with diabetes or on dyslipidemia medications were excluded. ΔTHR was derived using growth curve modeling and adjusted for age, sex, field centers, and principal components. GWAS used a linear mixed model accounting for familial relatedness. GWLS employed haplotype-based identity-by-descent estimation with 0.5 cM average spacing. Heritability of ΔTHR was moderate (46%). Our GWAS identified a …

Viral Kinetics Among Persons Living With Hiv (Plwh) On Dolutegravir-Based Antiretroviral Regimen: A Retrospective And Prospective Analysis From Selected Hiv Clinics In Ghana, Samuel Badu Nyarko, Joel Adu Twum, Aikins Sarpong Obeng, Helena Dede Djangba, Oksana Ryabinina, Foster Kyei, George Boateng Kyei, Nicholas Ekow Thomford

2020-Current year OA Pubs

BACKGROUND: Dolutegravir (DTG)-based antiretroviral therapy has demonstrated superior efficacy, tolerability, and durability when compared to other HIV treatment regimens. However, monitoring viral kinetics is critical for determining treatment efficacy and making sound judgments. The purpose of this study was to assess viral kinetics in people living with HIV (PLWH) on DTG-based ART and identify characteristics related to virologic response in the Cape Coast Metropolis, Ghana.

METHODS: Among people living with HIV (PLWH) attending HIV clinics between January 2020 and December 2023, a prospective and retrospective analysis of viral kinetics and clinical data were carried out. Data on viral loads, clinical …

A Clinical Practice Review Of Optimizing The Approach For Correction Of Thoracolumbar Deformity— When And How To Perform Anterior Releases And Fusion, Brian M. Phelps, Munish C. Gupta

2020-Current year OA Pubs

No abstract provided.

Piezo1-Mediated Calcium Influx Transiently Alters Nuclear Mechanical Properties Via Actin Remodeling In Chondrocytes, Jaquelin M Garcia-Castorena, Rosa Riester, Miranda Gamino-Ornelas, Nikitha Ada, Farshid Guilak, Marina Danalache

2020-Current year OA Pubs

Mechanosensation allows cells to generate intracellular signals in response to mechanical cues from their environment. Previous research has demonstrated that mechanical stress can alter the mechanical properties of the nucleus, affecting gene transcription, chromatin methylation, and nuclear mechanoprotection during mechanical loading. PIEZO1, a mechanically gated Ca

Vibrotactile Auricular Vagus Nerve Stimulation Alters Limbic System Connectivity In Humans: A Pilot Study, Kara M. Donovan, Joshua D. Adams, Ki Yun Park, Phillip Demarest, Gansheng Tan, Jon T. Willie, Peter Brunner, Jenna L. Gorlewicz, Eric C. Leuthardt

2020-Current year OA Pubs

Vibration offers a potential alternative modality for transcutaneous auricular vagus nerve stimulation (taVNS). However, mechanisms of action are not well-defined. The goal of this pilot study was to evaluate the potential of vibrotactile stimulation of the outer ear as a method for activating central brain regions similarly to established vagal nerve stimulation methods. Seven patients with intractable epilepsy undergoing stereotactic electroencephalography (sEEG) monitoring participated in the study. Vibrotactile taVNS was administered across five vibration frequencies (2, 6, 12, 20, and 40 Hz) following a randomized stimulation pattern with 30 trials per frequency. Spectral coherence during stimulation was analyzed across theta …

First Successful Ovarian Cortex Allotransplant To A Turner Syndrome Patient Requiring Immunosuppression: Wide Implications, Sherman J Silber, Sierra Goldsmith, Benjamin Rubinoff, Eduardo Kelly, Rowena Delos Santos, Anibal Melo, Daniel Brennan

2020-Current year OA Pubs

OBJECTIVE: To determine whether we can safely and successfully transplant an ovary tissue allograft from a nonidentical donor to her Turner syndrome sister.

DESIGN: Transplantation of cryopreserved ovary tissue, as well as fresh transplantation of ovarian tissue between identical twins, is now well established with numerous reported successful cases. However, there have not yet been any ovary transplants between nonidentical women requiring immunosuppression (ovary allotransplant). This could be a much more common indication for ovary tissue transplantation if safe and reliable immunosuppression were available.

PATIENT(S): A 20-year-old amenorrheic woman with nonmosaic 45-XO Turner syndrome requested ovary tissue transplantation from her …

Baseline Clinical Characterization Of Participants In The Accelerating Medicines Partnership Schizophrenia Program, Jean Addington, Daniel Mamah, Et Al.

2020-Current year OA Pubs

BACKGROUND: This paper focuses on the baseline clinical characterization of the participants in the Accelerating Medicines Partnership Schizophrenia (AMP SCZ) program. The AMP SCZ program is designed to investigate a wide array of clinical variables and biomarkers in a total of 2040 clinical high-risk (CHR) participants and 652 community control (CC) participants.

METHODS: The dataset analyzed includes 1642 individuals at clinical high risk for psychosis and 519 CCs. Key measures include the Positive Symptoms and Diagnostic Criteria for the Comprehensive Assessment of At-Risk Mental States Harmonized with the Structured Interview for Psychosis-Risk Syndromes, which determined CHR criteria and the severity …

Sample Ascertainment And Recruitment Sources In The Accelerating Medicines Partnership Schizophrenia Program, Jean Addington, Daniel Mamah, Et Al.

2020-Current year OA Pubs

BACKGROUND: This paper presents the recruitment sources of clinical high-risk (CHR) and community controls (CC) from the Accelerating Medicines Partnership Schizophrenia (AMP SCZ) program, which aims to study various clinical variables and biomarkers in 2040 CHR and 652 CC participants.

METHODS: A total of 1640 CHR and 514 CC had recruitment source data. The Positive Symptoms and Diagnostic Criteria for the Comprehensive Assessment of At-Risk Mental States Harmonized with the SIPS was utilized to assess CHR criteria and severity of attenuated psychotic symptoms (APSs), and the Global Functioning: Social Scale was used for social functioning. Participants were recruited through various …

Poor Sleep Is Common In Treatment-Resistant Late-Life Depression And Associated With Poorer Antidepressant Response: Findings From The Optimum Clinical Trial, Michael S B Mak, Marie Anne Gebara, Eric J Lenze, Daniel M Blumberger, Patrick J Brown, Pilar Cristancho, Alastair J Flint, Jordan F Karp, Helen Lavretsky, J Philip Miller, Charles F Reynolds 3rd, Steven P Roose, Benoit H Mulsant, Sarah T Stahl

2020-Current year OA Pubs

BACKGROUND: Adults with treatment-resistant late-life depression (TRLLD) have high rates of sleep problems; however, little is known about the occurrence and change in sleep during pharmacotherapy of TRLLD. This analysis examined: (1) the occurrence of insufficient sleep among adults with TRLLD; (2) how sleep changed during pharmacotherapy; and (3) whether treatment outcomes differed among participants with persistent insufficient sleep, worsened sleep, improved sleep, or persistent sufficient sleep.

METHODS: Secondary analysis of data from 634 participants age 60+ years in the OPTIMUM clinical trial for TRLLD. Sleep was assessed using the sleep item from the Montgomery-Asberg Depression Rating Scale at the …

Treatment Of Hereditary Hemorrhagic Telangiectasias With Sclerotherapy: A Case Series, Jenny Ji, Andrew M Peterson, Jay F Piccirillo

2020-Current year OA Pubs

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is characterized by abnormal blood vessel formation. One treatment for HHT-related arteriovenous malformations (AVMs) is sclerotherapy, which collapses the blood vessels by irritating the endothelial lining.

METHODS: This case series describes two HHT patients undergoing in-office sodium tetradecyl sulfate sclerotherapy for non-nasal telangiectasias and AVMs. The first patient had AVMs on the red lip while the second patient had an AVM and several telangiectasias on the tongue.

RESULTS: Both patients' AVMs required only one treatment visit and were no longer noticeable within a week. Neither of the patients had any side effects from treatment.

CONCLUSION: …